18-3129373-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_003803.4(MYOM1):c.2653C>G(p.Pro885Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,613,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_003803.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYOM1 | ENST00000356443.9 | c.2653C>G | p.Pro885Ala | missense_variant | Exon 18 of 38 | 1 | NM_003803.4 | ENSP00000348821.4 | ||
MYOM1 | ENST00000261606.11 | c.2506+2002C>G | intron_variant | Intron 17 of 36 | 1 | ENSP00000261606.7 | ||||
MYOM1 | ENST00000582016.1 | n.209C>G | non_coding_transcript_exon_variant | Exon 1 of 3 | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152160Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000802 AC: 2AN: 249256Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135218
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461708Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727136
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74330
ClinVar
Submissions by phenotype
not specified Uncertain:1
The p.P885A variant (also known as c.2653C>G), located in coding exon 17 of the MYOM1 gene, results from a C to G substitution at nucleotide position 2653. The proline at codon 885 is replaced by alanine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Hypertrophic cardiomyopathy Uncertain:1
In summary, this variant is a rare missense change with uncertain impact on splicing. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. The frequency data for this variant (rs764303814) in the population databases is unreliable, as metrics indicate poor quality at this position in the ExAC database. This variant has not been reported in the literature in an individual with a MYOM1-related disease. This sequence change replaces proline with alanine at codon 885 of the MYOM1 protein (p.Pro885Ala). The proline residue is weakly conserved and there is a small physicochemical difference between proline and alanine. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at